Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VIII. Toxins Affecting Hemoglobin and Oxidative Metabolism
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TABLE 27-7 Toxins Inducing Hemorrhage/Coagulopathy
Toxins Disease Onset Geography Species Affected
Anticoagulant rodenticides Chronic Worldwide All
Dicoumarol (moldy Melilotus alba ) Chronic Worldwide B, E, P
Drugs Chronic Worldwide All
Estrogen Chronic Worldwide All
Hepatotoxins Chronic Worldwide All
Pteridium aquilinum (bracken fern) Chronic Worldwide B, Cp, E, O, P
Trichothecenes Acute Worldwide All
Venoms Acute Worldwide All
Abbreviations: B, bovine; Cn, canine; Cp, caprine; E, equine; F, feline; O, ovine; P, porcine.
is usually insufficient to produce acute hemolytic crises,
and other factors, including decreased erythropoietin production,
likely play a larger role in the anemia seen with
chronic renal disease ( Stockham and Scott, 2002 ). The
anthelmintic, phenothiazine, may be acutely hemolytic in
sheep and horses. It also may induce primary photosensitization
as discussed under integumentary toxins. Zinc
intoxication in dogs can produce a severe intravascular
hemolysis ( Dziwenka and Coppock, 2003 ).
The venom of various, snakes including Crotalidae,
Elapidae, Hydrophidae, and Viperidae, contains a mixture
of toxins of which phospholipase A 2 (PLA 2 ) is an important
component. PLA 2 is directly lytic for erythrocytes and
may induce hemolysis, and for platelets and it may induce
hemorrhage and coagulopathy ( Cheville, 1988 ).
Basophilic stippling and inappropriate rubricytosis have
been associated with lead intoxication in dogs ( Stockham
and Scott, 2002 ) .
Additional toxins inducing hemorrhage ( Table 27-7 )
include dicumarol derived from moldy sweet clover
( Melilotus spp.) and the synthetic derivatives used as anticoagulant
rodenticides such as brodifacoum, bromadiolone,
diphacinone, fumarin, pindone, and warfarin. These
agents are vitamin K antagonists. Prothrombin (factor II),
and factors VII, IX, and X require vitamin K for their production.
The half-life of factor VII is approximately 4 to
6 h, whereas, half-lives of factors IX and X are approximately
14 to 18h, and for prothrombin the half-life is 40 h.
Therefore, prolongation of the one-stage prothrombin time
(PT) is thought to occur earliest, followed by prolongation
of the activated partial thromboplastin test (PTT). Vitamin
K antagonists do not affect fibrinogen or platelet numbers
initially but may eventually exhaust their supplies.
Excessive hemorrhage following slight trauma, epistaxis,
melena, and hematuria may occur with these intoxications
( Dodds, 1997 ). Testing for products of vitamin K antagonism
or absence (PIVKAs) may help to detect this intoxication.
This test is a modified PT assay, which detects
decreased activity of factors II, VII, and X. Though anticoagulant
rodenticide intoxication decreases the activity
of these factors, other diseases may also prolong this test;
thus this test is not specific for rodenticide intoxication
( Stockham and Scott, 2002 ).
Chronic hepatotoxicity in which hepatic mass is reduced
by 70% or more may result in sufficiently inadequate synthesis
of both clotting factors and their inhibitors to prolong
PT and PTT. Chronic cholestasis with interruption of
the enterohepatic circulation of bile salts also may result in
malabsorption of fat-soluble vitamin K producing a syndrome
similar to anticoagulant intoxication.
Toxins inducing pancytopenia include estrogen, Pteridium
aquilinum (bracken fern), and the trichothecene mycotoxins.
Insufficient numbers of platelets promote hemorrhage and
consumption coagulopathy ( Valli, 1993 ).
VIII . TOXINS AFFECTING HEMOGLOBIN
AND OXIDATIVE METABOLISM
Lead poisoning interrupts heme synthesis at the level of
formation of protoporphyrin and causes accumulation
of delta-aminolevulinic acid. Increased urinary excretion
of this metabolite indicates lead intoxication.
Toxins inducing oxidation of ferrous iron in hemoglobin
to ferric iron in methemoglobin ( Harvey, 1989 ) include
the herbicide sodium chlorate, the stalk parts of nitrateaccumulating
plants such as corn and wheat, hay grown on
heavily fertilized soils under drought conditions, fertilizer,
or water contaminated by fertilizers or organic material.
Wilted red maple leaves have also been reported to cause
methemoglobinemia, in addition to hemolysis, in horses
( Barr and Reagor, 2001 ). Ruminants are most susceptible to
the nitrate-accumulating plants Amaranthus spp. (pigweed),
Avena sativa (oats), Chenopodium spp. (lambsquarter),
Sorghum spp., and Triticum aestivum (wheat) because of the
ability of rumen microbes to reduce nitrate to the proximate